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Structural biology and engineering of neuronal signalling

Tuesday 22 January 2019, by Jonathan Elegheert


The interests of our team lay at the interface of structural biology, protein engineering, and cellular neuroscience. We aim to understand molecular principles of neuronal signalling in health and disease, and to translate these to the cellular and organismal level.

We use mammalian protein expression, protein chemistry, biophysical methods, X-ray crystallography and cryo-electron microscopy to study the interaction determinants and structures of [**synaptic protein complexes involved in neurodevelopmental disorders and neuronal disease*]. We use combinatorial methods and protein engineering to discover novel binders and manipulate protein sequence, structure and function, both to facilitate structural studies as well as enable therapeutic targeting of these complexes.

[*Join us! We currently have a 3-year postdoc position available!*]

[**TEAM LEADER: Jonathan Elegheert*]

After studying medicine (BSc) and biochemistry (MSc), I obtained my PhD in 2012 from Ghent University (Belgium), where I studied the structural biology of Colony-Stimulating Factor 1 (CSF-1) cytokine signalling in the lab of Prof. Savvas N. Savvides as a FWO (Research Foundation - Flanders) doctoral fellow. In 2012, I joined the Division of Structural Biology (STRUBI) at the University of Oxford (United Kingdom) as an EMBO- and Marie Curie Actions-funded postdoctoral fellow. There, I transitioned into molecular neuroscience and investigated the structural biology of synaptic protein complexes, in the lab of Prof. A. Radu Aricescu. In 2018, I joined the IINS as a team leader enabled by an Initiative of Excellence (IdEx) Junior Chair (University of Bordeaux) and a Neurocampus starting package (Conseil Régional de la Nouvelle Aquitaine). In 2019, I was recruited to the CNRS and I obtained an ERC Starting Grant.


Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins.

Elegheert J, Behiels E, Bishop B, Scott S, Woolley RE, Griffiths SC, Byrne EFX, Chang VT, Stuart DI, Jones EY, Siebold C, Aricescu AR.
Nature Protocols , 2018.

Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins.

Elegheert J, Cvetkovska V, Clayton AJ, Heroven C, Vennekens KM, Smukowski SN, Regan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR.
Neuron , 2017.

Structural basis for integration of GluD receptors within synaptic organizer complexes.

Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR.
Science , 2016.

Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.

Healey EG, Bishop B, Elegheert J, Bell CH, Padilla-Parra S, Siebold C.
Nature Structural & Molecular Biology , 2015.

Structural basis for extracellular cis and trans RPTPσ signal competition in synaptogenesis.

Coles CH, Mitakidis N, Zhang P, Elegheert J, Lu W, Stoker AW, Nakagawa T, Craig AM, Jones EY, Aricescu AR.
Nature Communications , 2014.

Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1.

Elegheert J, Bracke N, Pouliot P, Gutsche I, Shkumatov AV, Tarbouriech N, Verstraete K, Bekaert A, Burmeister WP, Svergun DI, Lambrecht BN, Vergauwen B, Savvides SN.
Nature Structural & Molecular Biology , 2012.

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